Issue Date: May 2, 2005
An herbal solution?
Philanthropists should seek the best and most affordable medicine for the patient. In "Bootstrapping via Philanthropy," C&EN cites One World Health figures when it says that "the current three-day malaria treatment containing artemisinin, a terpenoid compound laboriously extracted from Artemisia annua, is nearly 100% effective. But the plant is in short supply and the regimen, at about $2.40, is too costly for most poor regions. The hope is to develop treatment costing "well under" $1.00 per patient" (C&EN, Jan. 3, page 18). Perhaps in their high-tech approach, scientists will come up with high-cost answers.
The tea of the Artemisia herb is less than a dime a patient, all but free. The herb is an abundant weed along the Shenandoah and Potomac Rivers in Maryland, Virginia, and West Virginia, not at all in short supply. Furthermore, the whole herb is a polychemical "cocktail," containing at least half a dozen compounds shown to be synergic against malaria. The whole "natural cocktail" herb tea may not generate resistance as quickly as pure artemisinin or bipharmaceutical or tripharmaceutical cocktails.
But we must be sure that the natural cocktail is safe, efficacious, and less likely to generate resistance. Until then, we won't know whether the natural tea, at less than 20 cents per dose, is better. True philanthropists will doubtless insist on seeking the cheapest and most efficacious medicine, be it natural or synthetic. Any clinical trials for malaria comparing pure artemisinin with placebo should include a third arm, a tea of Artemisia annua (also known as Qing Hao or Sweet Annie), which has been used effectively for millennia for fevers. Until the tea is clinically compared, we cannot be sure that it isn't better or equal or only slightly inferior.
James A. Duke
We commend the gates foundation's recent $42.6 million investment to combat malaria, a disease that the World Health Organization (WHO) estimates kills a child every 20 seconds. Given the worldwide shortage of medication for this disease and the uncertainty that any one approach will be successful, we recommend additional strategies be investigated, including ones based on plant extracts that have been used for centuries, such as Artemisia annua, for which preliminary clinical studies suggest safety and efficacy.
Prompted by the Vietnam War, China consulted ancient texts for treatment for malaria. WHO's website says, "The Chinese herbal remedy Artemisia annua, used in China for almost 2,000 years, has been found to be effective against resistant malaria and could create a breakthrough in preventing almost one million deaths annually, most of them children, from severe malaria."
Artemisinin (isolated from A. annua) and analogs derived from it were later shown to be effective against resistant strains of the malaria parasite and are currently being used by WHO in combination with other agents, such as mefloquine, to prevent development of resistance.
Previously, when treated largely with quinine (isolated from the bark of the Cinchona tree), the malaria parasite developed resistance to quinine and several drugs modeled on the quinine structure (chloroquine and mefloquine), as well as to antifolates, such as sulphadoxine-pyrimethamine, which are the first- or second-line treatment in many African countries. Malaria will no doubt soon become resistant to Malarone (atovaquone-proguanil) if used as a single therapy on a large scale. Interestingly, the parasite is not resistant to whole Cinchona.
The development of standardized plant preparations or extracts based on artemisinin or additional bioactive compounds in A. annua could become a viable and low-cost solution, pending support for the needed pharmacological and clinical trials. The combination of bioactive compounds in this species may actually be synergistic to isolated and purified artemisinin, and the combination of compounds within the plant may preclude resistance that has occurred under single-compound therapies. Given the current shortage of artemisinin and the difficulties that many countries with high malarial incidence face in being able to afford treatment, exploring a plant-based therapeutic option within a modern scientific and clinical approach presents a compelling strategy.
We recommend that the Gates Foundation, public health officials, and the pharmaceutical industry support the needed pharmacological and clinical trials of standardized A. annua teas and other extract formulations. Should such studies show safety and efficacy, as some papers suggest, then further testing on product formulations and public policy would grow from that to incorporate such alternatives into health care policies. Clearly, such studies are low cost, would be rapid relative to biotechnological approaches now planned, and could easily be done with methodology acceptable to current clinical protocols. It's exciting to envision tropical countries being able to grow their own source of antimalarials and prepare such materials to ensure that a standardized medicinal regime is provided to those in need. The prospect of providing agricultural opportunities for the same countries is even more compelling. We need to consider multiple strategies that can each still meet the high standards we expect for any and all medicines.
Mike Benge, Washington, D.C.
Gordon Cragg, Frederick, Md.
Jorge Ferreira, Beaver, W.Va.
Janel Hopper, Palo Alto, Calif.
Jules Janick, West Lafayette, Ind.
W. John Kress, Washington, D.C.
Jim Simon, New Brunswick, N.J.
Gary Strobel, Bozeman, Mont.
Andrew Weil, Tucson, Ariz.
Merlin L. Willcox, Buckingham, England
F . David Doty should be commended for his letter to the editor "Biofuels versus hydrogen," which provides facts that dispute the claims of hydrogen advocates that hydrogen is a cheap and clean fuel (C&EN, March 14, page 6). It's about time someone provided some solid evidence to show the folly of the so-called hydrogen economy and the benefits of biofuels.
This brought to mind the fact that safety is another thing that we hear little about in discussions of hydrogen as a fuel for vehicles. At –253 °C, hydrogen has the lowest flash point of any fuel that is currently used or being considered. The flash point of a fuel is the temperature at which vapor given off will ignite when an external flame is applied under specified test conditions. Other common fuels have much higher flash points: propane, –104 °C; methanol, 11 °C; ethanol, 13 °C; and octane, 22 °C. Clearly, hydrogen is a very dangerous fuel to be considered for use in a consumer automobile.
When the first hydrogen-fueled automobile explodes in an accident and its occupants are vaporized, there will be an outcry not heard since the Challenger spacecraft explosion. As chemists, it seems to me that it's important to point out the danger before it's too late.
Joseph A. Castellano
San Jose, Calif.
I believe Doty's letter needs clarification. Forward thinking is needed, not status quo thinking. Let me explain: Just substituting one carbon-based fuel (biofuels) for another (gasoline) does not solve the global warming crisis. Hydrogen/fuel-cell automobiles are the answer.
Doty stated that today's cost of hydrogen is given as $100 per kg for small gaseous hydrogen users. Yet he also gives a figure of $6.00 per kg for liquid hydrogen, which requires large amounts of energy to compress and liquefy. This is quite a drop in cost. However, in the future we will not use this method. What will be used is solar/electrolysis at $3.50 per kg. In fact, when the price of gasoline reaches that level (possibly next year), it will be competitive with hydrogen fuel.
Doty talks about $4.00 per kg in distribution costs for liquid hydrogen to the filling stations. This will probably not be the way. Each station will have its own solar/electrolysis system to produce hydrogen locally. Even so, a gaseous hydrogen pipeline to each station from a solar/hydrogen facility outside the city could be done. So his $4.00-per-kg distribution cost for liquid hydrogen goes out the window. In fact, it is known that pumping gaseous hydrogen 1,000 miles is 50% cheaper than moving the same amount of electricity that distance on an equivalent energy unit basis. When we run out of natural gas, all those pipelines crisscrossing the U.S. can be conveniently used to transport hydrogen gas. Hence, liquid hydrogen will not be pumped in underground pipelines in the distant future.
The recent crash tests of rear-mounted automobile hydrogen fuel tanks shows less of a hazard than gasoline for this simple reason: Hydrogen is lighter and goes upward; it does not stay on the ground like gasoline.
If there is a death knell for hydrogen, why are so many auto and bus manufacturers building hydrogen/fuel-cell autos as well as hydrogen/internal combustion automobiles? Why is Canada building a huge liquid hydrogen facility to generate hydrogen from their abundant water power and shipping the hydrogen to Germany? Last year, Iceland stated that the national goal is to be the first hydrogen-powered country. Japan is building liquid hydrogen ocean tankers. The world alternative energy market is more than $1.5 billion and grew 17% last year. I believe we will see a solar/hydrogen economy soon.
San Marcos, Calif.
If we could, in one stroke, convert all fossil energy consumption (oil, gas, coal, and so on) to bio-derived energy sources (biomass sources for carbon), the steady increase in the percent of carbon dioxide in the atmosphere would be completely eliminated. Carbon for biomass comes from the air, so there would be no net increase in atmospheric carbon load. The technology is available. All that is lacking is the will to do it and the leadership to encourage and sustain that will.
Doty's recent letter presents a most compelling argument for abandoning the current fascination with hydrogen and focusing our considerable efforts on other topics. After 30 years in the chemical and pharmaceutical industries, I can certainly appreciate Doty's and others' quantitative analysis of the various energy alternatives. I believe that nuclear fission and fusion, the only alternative to the options proposed by Doty, will never be accepted by either the general or political populace.
I submit that the scientific community, and particularly the chemical community, should promulgate these and further analyses for the education of the public, including our elected representatives and other stakeholders in this issue.
Rudolph H. Stehl
Issues with dosing
I would like to make some comments about drugs and their potential harmful side effects. Depending on the acuity of their disease, patients have to take a cure either at home or at the hospital. But in both of these locations, the main problem that occurs results from the intervariability of patients who respond in a different manner to the drug.
Without speaking of modern painkillers, and considering only the simple case of aspirin, we can see that if one tablet is enough to relieve the headache of one patient, two of them are necessary for another, while half a tablet will be too much for a third because of nose bleeding. Some drugs exhibit quite different pharmacokinetic parameters according to patients, with the apparent plasmatic volume varying by 150% around its mean value, while the values of the half-life can lie within a 400% range.
From these data, it is clear that for a drug having a narrow therapeutic index, the therapist has to know the patient and the patient's response to the drug in order to adapt the therapy (the amount and frequency of the dosage) to reduce side effects, if not avoid them. These side effects are sometimes as bad as the original disease. At the hospital, from the first intravenous injection, these two parameters can be evaluated by making analyses at two different times, adjusting the treatment afterward if necessary.
At home, where tablets are of unique size and not always divisible, there is no way to adapt the dose, as dose frequency is a difficult way to resolve the problem. But some galenic forms, even when they are able to sustain the drug release, are presented in such a way that they can be divided in equal parts. Moreover, physicians are often unaware of the limited reliability of patients; in the U.S. and Europe, 40–60% of patients do not comply with the scheduled regimen. They omit a dose and, even worse, correct this omission by doubling the dose afterward.
J. M. Vergnaud
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